2型糖尿病患者外周血CD14+CD16+单核细胞水平及巨噬细胞STAT3蛋白表达的研究

目的 研究T2DM患者外周血CD14+ CD16+单核细胞数和血清IL-6、TGF-β的水平,及患者血清和IL-6孵育的THP-1单核细胞源性巨噬细胞STAT3、p-STAT3的蛋白表达,以了解炎症性免疫反应在T2DM大血管病变中的可能作用. 方法 对42例T2DM(T2DM组)患者和35名健康体检者(NC组)采用外周血流式细胞术检测外周血单核细胞CD14+ CD16+的表达,并分离其外周血血清.采用ELISA检测血清中细胞因子IL-6及TGF-β的浓度,免疫比浊法检测血清中高敏C反应蛋白(hsC-RP)水平,血清和IL-6孵育THP-1单核细胞源性巨噬细胞,采用Western blot检测其STAT3和p-STAT3的蛋白表达. 结果 T2DM组外周血CD14+ CD16+单核细胞数高于NC组(P＜0.01),且与血清hsC-RP和IL-6水平呈正相关(r=0.462、0.495,P＜0.01),与TGF-β水平无相关性(P＞0.05).T2DM组24 hUAlb水平、大血管病变发病率及THP-1单核细胞源性巨噬细胞p-STAT3的蛋白表达均高于NC组(P＜0.01). 结论 T2DM患者体内可能存在单核/巨噬细胞功能异常,其可能参与了T2DM患者体内免疫炎症反应,从而导致了T2DM及其血管病变的发生发展,作用机制可能与STAT3信号通路的激活有关.     

有关2型糖尿病相关炎症通路的研究

目的该文主要为了研究2型糖尿病患者外周血巨噬细胞中是否有ERK及STAT3通路的磷酸化激活。方法收集30例2型糖尿病患者及30名健康体检者的病例资料,提取两管肘静脉血。1离心收集上清液用ELISA法检验TNF-α及IL-6的分泌水平;2收集单核细胞,培养出巨噬细胞;3提取蛋白,Western blot法检测ERK、p-ERK、STAT3及p-STAT3的表达情况。结果 1与对照组比较而言,病例组中炎性因子TNF-α及IL-6的分泌显著增多,差异有统计学意义(P0.05);2糖尿病患者外周血巨噬细胞中普遍存在ERK及STAT3通路的磷酸化激活,但两种蛋白的总体表达水平却未见异常,半定量分析后发现,药物组中磷酸化蛋白/总蛋白的含量比值与对照组中两者比值比较差异具有统计学意义(P0.05)。结论 ERK及STAT3两条通路均参与了2型糖尿病的发病过程。     

NOD1/RIP2信号通路对巨噬细胞炎性活化的作用

目的以人单核细胞株THP-1为基础,探讨NOD1/受体相互作用蛋白2(RIP2)信号通路对巨噬细胞炎性活化及表型的影响。方法用160 nmo L/L的佛波酯(PMA)将THP-1单核细胞诱导分化成巨噬细胞,分别用10、25和50 mg/L浓度的氧化型低密度脂蛋白(ox-LDL)刺激THP-1源性巨噬细胞24 h,以空白组为对照组。应用RT-PCR法检测NOD1和RIP2的mRNA表达情况;应用Western blot法检测NOD1和RIP2的蛋白表达情况;应用ELISA法检测细胞培养液中单核细胞趋化蛋白1(MCP-1)和巨噬细胞移动抑制因子(MIF)的分泌;应用流式细胞学检测巨噬细胞表面抗原CD16、CD68表达。结果 ox-LDL能以剂量依赖的方式激活THP-1源性巨噬细胞中NOD1/RIP2信号通路,随着ox-LDL刺激浓度的增加,NOD1、RIP2的mRNA和蛋白表达水平升高(P0.05)。NOD1/RIP2信号通路激活后能使细胞培养物上清液中炎症因子MIF和MCP-1的表达增加,随着ox-LDL刺激浓度的增加,MCP-1和MIF的分泌增多(P0.05)。NOD1/RIP2信号通路激活后能改变巨噬细胞表面抗原CD16、CD68的表达,随着ox-LDL刺激浓度的变化,巨噬细胞表面抗原CD16/CD68的平均荧光强度发生变化,其中50 mg/L组能显著下调CD16/CD68的表达(P0.01)。结论巨噬细胞中NOD1/RIP2信号通路能被ox-LDL以剂量依赖的方式激活,NOD1/RIP2信号通路激活后能导致巨噬细胞的炎性活化及其表型变化,这可能是其参与动脉粥样硬化形成和发展过程的主要机制。     

沙眼衣原体pORF5质粒蛋白激活p38MAPK和NALP3信号通路调控THP-1细胞IL-1β分泌的研究

目的研究沙眼衣原体(Chlamydia trachomatis,Ct)pORF5质粒蛋白诱导THP-1细胞产生IL-1β的分子机制,为阐明Ct致病机制提供实验依据。方法将原核表达重组体pGEX-6p/pORF5转化大肠埃希菌,表达并纯化GST-pORF5融合蛋白,融合蛋白经蛋白酶酶切后制备不含GST标签的pORF5蛋白;用不同浓度的pORF5蛋白体外刺激THP-1细胞,ELISA测定不同时间IL-1β水平;分别用NALP3siRNA、ASC siRNA、Caspase-1抑制剂和p38抑制剂预处理THP-1细胞,再用pORF5蛋白刺激THP-1细胞24h,ELISA测定IL-1β含量,Real-time PCR测定IL-1β和NALP3炎性体mRNA的表达,Western blot分析Caspase-1的表达及p38磷酸化水平。结果 pORF5蛋白以剂量和时间依赖的方式刺激THP-1细胞产生IL-1β,24μg/ml pORF5蛋白刺激24h时IL-1β的表达水平达到峰值(495.1±55.5pg/ml);pORF5蛋白能促进THP-1细胞中NALP3炎性体mRNA的表达;NALP3-siRNA、ASC-siRNA及Caspase-1抑制剂预处理THP-1细胞后,IL-1β分泌量分别降低37.7%、71.3%和40.1%;p38抑制剂能降低NALP3炎性体mRNA及IL-1β分泌量(P0.01),但抑制NALP3炎性体后p38磷酸化水平未受影响(P0.05)。结论 pORF5质粒蛋白通过激活p38MAPK和NALP3信号通路共同调控IL-1β的产生和分泌。     

川芎嗪对刀豆蛋白A诱导的小鼠肝纤维化JAK2/STAT3信号通路的影响

目的为探究JAK2/STAT3信号通路与炎性因子白细胞介素6、1β、10(interleukin-6、1β、10)的关系,IL-6、IL-1β、IL-10是否参与刀豆蛋白A(ConA)诱导的小鼠肝纤维化过程以及川芎嗪对其的影响。方法 BALB/C小鼠随机分为5组,正常对照组(A组)10只;ConA模型(B组)15只;川芎嗪低剂量(100 mg/kg)组(C组)15只;川芎嗪中剂量(200 mg/kg)组(D组)15只,川芎嗪高剂量(800 mg/kg)组(E组)15只。通过实时荧光定量PCR检测IL-6mRNA、IL-1βmRNA和IL-10mRNA的表达水平;Western-blot检测JAK2、STAT3和p-JAK2、p-STAT3的表达情况。结果与模型组相比,小鼠经不同剂量川芎嗪干预8周后,IL-6mRNA和IL-1βmRNA表达水平均降低,且与给药剂量呈相关性;IL-10mRNA表达水平升高,且与给药剂量呈相关性;p-JAK2、p-STAT3蛋白表达均降低,且下降程度与给药呈剂量相关性;JAK2和STAT3蛋白表达变化不明显。结论川芎嗪可能通过JAK2/STAT3信号通路及炎性因子IL-6、IL-1β、IL-10对ConA诱导的小鼠肝纤维化产生保护作用。     

老年糖尿病患者应用阿司匹林反应性研究

目的研究老年糖尿病患者应用阿司匹林的反应及影响因素。方法采用光学法血小板聚集,分别应用花生四烯酸（arachidonicacid,AA）、二磷酸腺苷（adenosinediphosphate,ADP）作为诱导剂检测199例老年糖尿病患者血小板功能;全自动生化仪检测空腹、餐后2h血糖、血脂、肾功能;高压液相法测定糖化血红蛋白指标。运用real—timePCR、WesternBlot检测循环血中单核细胞环氧化酶一2（cyclooxygenase-2,COX-2）mRNA、蛋白表达水平;同时检测人单核细胞（THP-1）在不同时间（12h、24h）和不同葡萄糖浓度（5．6mmol／L、11．1mmol／L、22．2mmol／L）情况下COX-2mRNA的表达量。结果非阿司匹林敏感（notaspirinsensitive,NAS）组空腹血糖、糖化血红蛋白水平高于敏感组;糖化血红蛋白未达标组NAS发生率高于达标组;糖尿病病程长的组NAS发生率更高。空腹血糖、糖化血红蛋白是NAS的相关危险因素。NAS组外周血单核细胞中COX-2mRNA表达量、蛋白表达率高于阿司匹林敏感组（aspirinsensitive,ASo葡萄糖刺激人单核细胞（THP-1）COX-2mRNA表达增加,且所用葡萄糖浓度越高、时间越长COX-2mRNA表达量越高。结论空腹血糖、糖化血红蛋白是老年糖尿病患者阿司匹林不敏感独立的危险因素。高糖刺激COX-2表达增加,这可能是糖尿病患者阿司匹林不敏感发生率增高的原因之一。     

甘草查尔酮A对THP-1巨噬细胞促炎因子表达的影响——依赖于TLR-4/NF-κB炎症信号通路

目的探讨甘草查尔酮A(Lico A)对脂多糖(LPS)诱导的人急性单核细胞白血病细胞株(THP-1)巨噬细胞相关炎症因子表达的影响。方法用100μg/L佛波酯(PMA)诱导THP-1细胞48 h,使其分化为巨噬细胞后,分为空白组、LPS组和LPS+不同浓度Lico A组(20、10、5 mg/L)。用酶联免疫吸附法检测细胞培养液中白细胞介素1β(IL-1β)、白细胞介素6(IL-6)和肿瘤坏死因子α(TNF-α)的含量,实时定量PCR检测Toll样受体4(TLR-4)和核因子κB(NF-κB)m NRA水平,采用Western blot检测TLR-4、NF-κB、IκB激酶(IKKα)、磷酸化IKB-α(p-IKB-α)、环氧合酶2(COX-2)和一氧化氮合酶(i NOS)蛋白表达水平。结果 LPS诱导THP-1巨噬细胞后,IL-1β、IL-6、TNF-α水平升高,Lico A可降低LPS诱导引起的IL-1β、IL-6和TNF-α表达水平升高。LPS刺激后TLR-4 m NRA及蛋白表达增加,NF-κB活化,Lico A可拮抗以上作用,阻止NF-κB活化。结论 Lico A可通过TLR-4/NF-κB通路抑制LPS诱导的THP-1巨噬细胞炎性反应。     

大鼠血管平滑肌细胞中以COX-2/JAK2/STAT3为靶向的信号转导分子调控机制的研究

目的:研究转录信号转导子和激活子3(STAT3)信号转导通路与选择性环氧化酶2(COX-2)抑制剂调控血管平滑肌细胞(VSMC)增殖凋亡的关系,明确COX-2抑制剂作用的细胞内信号转导机制。方法:将选择性COX-2抑制剂NS-398,作用于鼠VSMCs,运用MTT法检测细胞增殖状态;流式细胞仪观察NS-398对细胞凋亡的影响,进一步用RT-PCR检测药物作用前后VSMCs中COX-2mRNA表达;Westernblot检测药物作用前后STAT3通路相关蛋白JAK2、STAT3、CyclinD1、Bcl-2的表达及磷酸化活性。结果:鼠VSMCs中COX-2mRNA呈高表达,NS-398呈时间、剂量依赖性方式抑制VSMCs细胞增殖,促进其凋亡。加入NS-398的VSMCs中COX-2mRNA表达水平显著下降(P<0·01)。同时P-JAK2、P-STAT3、CyclinD1、Bcl-2表达水平随作用时间延长而下降(P<0·01)。结论:选择性COX-2抑制剂NS-398对VSMCs作用与COX-2mRNA水平相关,癌基因Stat3信号转导通路调控了NS-398对VSMCs作用的细胞内信号转导机制,最终通过其下游靶基因CyclinD1、Bcl-2影响VSMCs的增殖与凋亡。     

黄芩素对大鼠心肌缺血-再灌注损伤的保护作用及对Janus激酶-信号转导与转录激活分子信号通路的影响

目的探讨黄芩素对大鼠心肌缺血-再灌注(I/R)损伤的作用及对Janus激酶(JAK)-信号转导与转录激活分子(STAT)信号通路的影响。方法 50只大鼠随机分为正常对照(C)组、假手术对照(S)组、模型(IR)组、黄芩素低剂量(L)组和高剂量(H)组,每组10只。对IR组、L组、H组采用冠脉前降支结扎释放制备I/R损伤模型,L组、H组黄芩素分别腹腔注射给药0.4和1.2 mg/(kg·d),连续给药7 d。氯化三苯基四氮唑(TTC)法评价心肌梗死率,酶联免疫吸附试验(ELISA)检测血清中肿瘤坏死因子(TNF)-α、白细胞介素(IL)-1β、IL-6水平,实时荧光定量PCR及Western印迹分别检测心肌组织中Bcl-2、Bax、JAK2和STAT3基因mRNA及蛋白相对表达水平。结果 IR组、L组、H组I/R损伤造模成功,C组和S组心肌正常。与S组相比,IR组、H组、L组均出现不同程度灰白色坏死心肌,且血清中TNF-α、IL-1β、IL-6水平明显增加,Bax、JAK2和STAT3基因mRNA及蛋白表达升高,而Bcl-2基因mRNA及蛋白表达降低,差异均有统计学意义(P0.05)。与IR组比,H组、L组灰白色坏死心肌均明显减少,血清中TNF-α、IL-6水平相对降低,Bax、JAK2和STAT3基因mRNA及蛋白表达相对降低,而Bcl-2基因mRNA及蛋白表达相对升高,差异均有统计学意义(均P0.05)。与L组相比, H组灰白色坏死心肌有所减少,血清中TNF-α、IL-6水平降低,Bax、JAK2和STAT3基因mRNA及蛋白表达降低,而Bcl-2基因mRNA及蛋白表达升高,差异均有统计学意义(均P0.05)。结论黄芩素对大鼠I/R损伤具有保护作用,其机制可能与抑制JAK-STAT信号通路有关。     

糖蛋白基因表达对人永生化角质形成细胞株活性的影响及机制

目的探讨糖蛋白(GP)基因表达对人永生化角质形成细胞株活性的影响及相关机制。方法体外培养HaCaT人永生化表皮细胞,设计并合成3组GP130 siRNA序列,转染HaCaT细胞,从mRNA和蛋白质水平筛选并验证最佳siRNA序列和浓度。分别于转染HaCaT细胞24 h、48 h时,使用噻唑蓝(MTT)法、流式细胞术检测细胞增殖和增殖周期;实时荧光定量聚合酶链反应(PCR)、Western印迹检测白细胞介素(IL)-6 mRNA和蛋白表达。结果培养24 h时siRNA1组、siRNA-nc组、空白对照组HaCaT细胞增殖率之间差异无统计学意义(P0.05);培养48 h时siRNA1组HaCaT细胞增殖率明显低于siRNA-nc组、空白对照组(P0.05)。培养24 h时G1期、S期、G2期的HaCaT细胞水平在siRNA1组、siRNA-nc组、空白对照组之间差异无统计学意义(P0.05);培养48 h时siRNA1组G1期HaCaT细胞数量明显高于siRNA-nc组、空白对照组,S期和G2期细胞数量明显低于siRNA-nc组、空白对照组(P0.01);培养48 h时siRNA1组G1期细胞数量明显高于培养24 h时,G2期细胞数量明显低于培养24 h时(P0.01)。培养24 h时siRNA1组、siRNA-nc组、空白对照组IL-6 mRNA及蛋白表达水平之间差异无统计学意义(P0.05);培养48 h时siRNA1组IL-6 mRNA及蛋白表达水平明显低于siRNA-nc组、空白对照组(P0.01);培养48 h时siRNA1组IL-6 mRNA及蛋白表达水平明显低于培养24 h时(P0.01)。结论下调GP130基因表达可抑制HaCaT细胞增殖,影响细胞增殖周期;其机制可能通过抑制IL-6表达,经Janus激酶(JAK)-信号转导与转录激活子(STAT)3信号通路调控HaCaT细胞增殖。     

胰岛素瘤的解剖分布特点分析

目的胰岛素瘤是最常见的胰腺神经内分泌肿瘤，因其临床表现多样，导致诊断困难。影像学诊断尤其是超声内镜(EUS)在胰岛素瘤的诊断中起着重要作用，拥有较高的敏感性和特异性。本研究拟通过明确胰岛素瘤的解剖分布特点，以期有助于提高影像学的诊断准确率和降低漏诊率，尤其是在教育和培训实践中对于EUS的学习者更具有指导价值。 方法回顾性分析解放军总医院第一医学中心病案资料数据库1993年1月至2019年11月经外科手术、病理确诊为胰岛素瘤的患者的临床资料，检索方法采取搜索术后病理诊断为"胰岛素瘤"的病例，通过查阅病例的方法，提取出胰岛素瘤的大小和解剖分布等数据，进一步分析其特点。 结果共检索到确诊为胰岛素瘤的患者116例，其中，男45例、女71例，年龄13～76岁，平均年龄(44.4±14.85)岁。胰岛素瘤单发110例(94.8%)、多发6例(5.2%)。位置分布：头颈部46例(39.7%)，单发45例、多发1例；体尾部68例(58.6%)，单发65例、多发3例；全胰腺多发2例(1.7%)。病变大小特点：最大径0.4～3.4 cm，平均大小(1.53±0.58)cm。≤1 cm 29例、>1 cm而≤1.5 cm41例、>1.5 cm而≤2.0 cm28例，≤3 cm 15例，>3 cm 3例。年龄与肿瘤的大小相关，≤44岁患者肿瘤平均大小为(1.36±0.51)cm、>44岁患者肿瘤平均大小为(1.70±0.60)cm，P<0.05。头颈部的肿瘤大于体尾部的肿瘤，头颈部肿瘤平均大小(1.66±0.63)cm，体尾部(1.42±0.52)cm，P<0.05。 结论胰岛素瘤在胰腺体尾部较头颈部更好发；绝大多数单发，但可以全胰腺多发；多数小于1.5 cm，肿瘤的大小与患者年龄和肿瘤的解剖分布相关。     

Pathogenesis of carcinoma of the papilla of Vater

Most adenomas and carcinomas of the small intestine and extrahepatic bile ducts arise in the region of the papilla of Vater. In familial adenomatous polyposis (FAP) it is the main location for carcinomas after proctocolectomy. In many cases symptoms due to stenosis lead to diagnosis at an early tumor stage. In about 80%, curative intended resection is possible. Operability is the most relevant prognostic factor. Most ampullary carcinomas resp. carcinomas of the papilla of Vater develop from adenomatous or flat dysplastic precursor lesions. They can be sited in the ampulloduodenal part of the papilla of Vater, which is lined by intestinal mucosa. They also can develop in deeper parts of the ampulla, which are lined by pancreaticobiliary duct mucosa. Intestinal-type adenocarcinoma and pancreaticobiliary-type adenocarcinoma represent the main histological types of ampullary carcinoma. Furthermore, there exist unusual types and undifferentiated carcinomas. Many carcinomas of intestinal type express the immunohistochemical marker profile of intestinal mucosa (keratin 7?, keratin 20+, MUC2+). Carcinomas of pancreaticobiliary type usually show the immunohistochemical profile of pancreaticobiliary duct mucosa (keratin 7+, keratin 20?, MUC2?). Even poorly differentiated carcinomas, as well as unusual histological types, may conserve the marker profile of the mucosa they developed from. These findings underline the concept of histogenetically different carcinomas of the papilla of Vater which develop either from intestinal- or from pancreaticobiliary-type mucosa of the papilla of Vater. Molecular alterations in ampullary carcinomas are similar to those of colorectal as well as pancreatic carcinomas, although they appear at different frequencies. In future studies, molecular alterations in ampullary carcinomas should be correlated closely with the different histologic tumor types. Consequently, the histologic classification should reflect the histogenesis of ampullary tumors from the two different types of papillary mucosa.     

Lack of correlation of degree of villous atrophy with severity of clinical presentation of coeliac disease

BACKGROUND AND AIM: Both the clinical presentation and the degree of mucosal damage in coeliac disease vary greatly. In view of conflicting information as to whether the mode of presentation correlates with the degree of villous atrophy, we reviewed a large cohort of patients with coeliac disease. PATIENTS AND METHODS: We correlated mode of presentation (classical, diarrhoea predominant or atypical/silent) with histology of duodenal biopsies and examined their trends over time. RESULTS: The cohort consisted of 499 adults, mean age 44.1 years, 68% females. The majority had silent coeliac disease (56%) and total villous atrophy (65%). There was no correlation of mode of presentation with the degree of villous atrophy (p=0.25). Sixty-eight percent of females and 58% of males had a severe villous atrophy (p=0.052). There was a significant trend over time for a greater proportion of patients presenting as atypical/silent coeliac disease and having partial villous atrophy, though the majority still had total villous atrophy. CONCLUSIONS: Among our patients the degree of villous atrophy in duodenal biopsies did not correlate with the mode of presentation, indicating that factors other than the degree of villous atrophy must account for diarrhoea in coeliac disease.     

Demonstration of the mechanism of action of biguanides

Summary Palmitic acid oxidation in rat diaphragm homogenate is depressed by biguanide concentrations that are still incapable of inhibiting oxidative phosphorylation. Glucose oxidation is not directly effected by the same biguanide concentrations: however, the inhibitory effect of palmitic acid on glucose oxidation is partly removed by biguanides. Inhibition of fatty acid oxidation, which accounts for most of the metabolic effects caused by these drugs, can be regarded as the fundamental mechanism of action of biguanides. There is some evidence suggesting that these drugs might interact with carnitine, thus preventing long-chain fatty acids from being transported across the mitochondrial membrane to the site of oxidation. Traduzione a cura degli AA.     

血吸虫童虫生长发育及其机制的研究进展

血吸虫童虫是宿主免疫系统攻击的重要靶标,包括皮肤型、肺型和肝门型童虫。宿主分子对童虫生长发育具有重要作用。童虫生长发育机制包括免疫调节、信号转导、性别发育及凋亡等。肌动蛋白、组织蛋白酶、烯醇化酶和葡萄糖基转移酶等分子为血吸虫童虫生长发育的重要分子。本文对血吸虫童虫生长发育及其机制的研究进展做一综述。     

124例耐多药结核分枝杆菌基因突变特征分析

目的对临床分离的耐多药结核分枝杆菌相关基因的突变特征进行分析。方法对124例耐多药结核分枝杆菌以及50株敏感株的耐药相关基因(包括异烟肼inh A、kat G、oxyR-ahp C间隔区以及利福平rpo B)进行序列测定,分析其基因突变情况。结果异烟肼耐药inh A基因突变率为14.5%;kat G基因突变率为70.2%(87/124),主要位于315位;oxyR-ahp C间隔区突变率为15.3%;inh A、kat G两种基因同时突变率75.0%,三种基因同时突变率为89.5%。利福平rpo B基因突变的检出率高达95.2%,突变主要发生在531、526、516位点。结论我省耐多药菌异烟肼耐药相关基因最常见突变为kat G 315、inh A C-T(-15)、axyR-ahp C间隔区(-10)C-T,利福平为rpo B531、526、516。结合MDR-TB耐药相关基因的特征分析,可以建立一种快速、准确、特异的适合于我省的检测结核菌耐多药性的新方法。     

Assessment of quality of life of parents of children with juvenile chronic arthritis

The aim of the study was to assess the quality of life (QOL) and the psychological status of parents of children with juvenile chronic arthritis (JCA). The QOL, anxiety and depression of the parents of 28 children with JCA were evaluated and compared to those of the parents of 28 healthy children. Mothers of JCA children and mothers of healthy children reported similar QOL. The reported anxiety and depression levels were similar for mothers and fathers in both groups. The parents of children with pauciarticular-type JCA reported lower QOL and higher levels of anxiety and depression than the parents of children with other types, namely polyarticular and systemic JCA. These findings may be explained by the fact that the pauciarticular patients had shorter disease duration and were less frequently seen in the outpatient clinic. The QOL of mothers of children with JCA was found to be slightly impaired in the group of children with pauciarticular JCA. Future larger studies are needed to confirm these results, as the number of subjects in the three groups was rather low. Received: 26 September 2001 / Accepted: 8 February 2002     

Numerical Simulation of the Effect of Rate of Change of Glucose on Measurement Error of Continuous Glucose Monitors

Background

A 5-day in-patient study designed to assess the accuracy of the FreeStyle Navigator® Continuous Glucose Monitoring System revealed that the level of accuracy of the continuous sensor measurements was dependent on the rate of glucose change. When the absolute rate of change was less than 1 mg•dl⁻¹•min⁻¹ (75% of the time), the median absolute relative difference (ARD) was 8.5%, with 85% of all points falling within the A zone of the Clarke error grid. When the absolute rate of change was greater than 2 mg•dl⁻¹•min⁻¹ (8% of the time), the median ARD was 17.5%, with 59% of all points falling within the Clarke A zone.

Method

Numerical simulations were performed to investigate effects of the rate of change of glucose on sensor measurement error. This approach enabled physiologically relevant distributions of glucose values to be reordered to explore the effect of different glucose rate-of-change distributions on apparent sensor accuracy.

Results

The physiological lag between blood and interstitial fluid glucose levels is sufficient to account for the observed difference in sensor accuracy between periods of stable glucose and periods of rapidly changing glucose.

Conclusions

The role of physiological lag on the apparent decrease in sensor accuracy at high glucose rates of change has implications for clinical study design, regulatory review of continuous glucose sensors, and development of performance standards for this new technology. This work demonstrates the difficulty in comparing accuracy measures between different clinical studies and highlights the need for studies to include both relevant glucose distributions and relevant glucose rate-of-change distributions.     

氯硝柳胺悬浮剂的毒性评价

目的评价氯硝柳胺悬浮剂的毒性，为现场大规模应用灭螺提供依据。方法按照中华人民共和国国家标准GB 15670-1995《农药登记毒理学试验方法》和鱼类毒性试验方法进行。结果经口、经皮肤的LDso雌、雄性大鼠均>5 000 mg/kg，经呼吸道的LCso雌、雄性大鼠均>5 000mg/m3，该药经口、经皮肤、经呼吸道毒性均属微毒类药物；兔眼用药后，观察期内无不良反应，对眼无刺激性；皮肤用药后对皮肤无刺激性。与氯硝柳胺原药、氯硝柳胺乙醇胺盐原药和氯硝柳胺乙醇胺盐可湿性粉剂相比，氯硝柳胺悬浮剂对鱼急性毒性最低。结论氯硝柳胺悬浮剂属微毒类药物，对鱼的毒性低于其乙醇胺盐可湿性粉剂，适合于现场应用。     

Study of constancy of hydrogen-consuming flora of human colon

The constancy of the hydrogen consuming flora of the human colon was studied in 15 healthy subjects via two measurements obtained 18 to 36 months apart. Hydrogen disappearance rate and the major products of H₂-consuming bacteria, methane and sulfide, were measured during incubation of fecal homogenates with excess hydrogen and sulfate. In 11/15, the hydrogen consumption rate and the predominant hydrogen-consuming pathway (methanogenesis, sulfate reduction, or neither) remained constant. However, major shifts in these pathways were observed in four subjects, with two losing and two gaining the ability to produce methane. Methanogenesis was associated with the highest hydrogen consumption rate. This study demonstrates that clinically unrecognizable, major alterations of the colonic flora occur in healthy subjects. Understanding of the factors responsible for these alterations might allow for therapeutic manipulation of the colonic flora.Supported in part by the Department of Veterans Affairs and NIDDKD RO1 DK 13309-25.